Compositions and methods for treatment of peripheral vascular disease

Abstract

The present invention relates to compositions and methods for the treatment of peripheral vascular disease (PVD). In particular, the invention provides compositions and methods for treatment of critical limb ischemia, and related diseases, disorders or conditions, based on the use of angiotensin-(1-7) peptides or functional equivalents, analogs or derivatives, angiotensin-(1-7) receptor agonists, ACE2 and / or ACE2 activators.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application claims priority from U.S. provisional patent application Ser. No. 61 / 597,223, filed Feb. 10, 2012, and U.S. provisional patent application Ser. No. 61 / 720,301, filed Oct. 30, 2012, the disclosures of which are hereby incorporated in their entirety.SEQUENCE LISTING[0002]The present specification makes reference to a Sequence Listing submitted electronically as an ASCII .txt file named “Sequence_Listing” on May 16, 2013. The .txt file was generated on May 15, 2013 and is 39 KB in size. The entire contents of the Sequence Listing are herein incorporated by reference.BACKGROUND[0003]Peripheral vascular disease (PVD) is generally characterized by partial or complete obstruction of vasculature outside the heart or brain, and can result from atherosclerosis, inflammatory processes leading to stenosis, embolism, or thrombus formation, among others. Peripheral artery disease (PAD) is a form of PVD in which there is a partial or to...

AI Technical Summary

Benefits of technology

[0012]In various embodiments, the angiotensin (1-7) peptide contains one or more chemical modifications to increase protease resistance, serum stability and / or bioavailability. In some embodiments, the one or more chemical modifications include pegylation.

[0015]In various embodiments, the angiotensin (1-7) peptide induces and / or increases angiogenesis and / or vascularization in the one or more tissues outside the heart and brain. In certain embodiments, the angiotensin (1-7) peptide decreases and / or delays cell death in the one or more tissues outside the heart and brain. In some embodiments, the cell death is apoptotic or necrotic. In certain embodiments, the angiotensin (1-7) peptide increases and / or enhances cell survival in the one or more tissues outside the heart and brain.

[0016]In various embodiments, the therapeutically effective amount of the angiotensin (1-7) peptide is sufficient to decrease partial or total blockage of blood flow to the one or more tissues outside the heart and brain. In some embodiments, the therapeutically effective amount of the angiotensin (1-7) peptide is sufficient to decrease or delay tissue damage in the one or more tissues outside the heart and brain. In certain embodiments, the therapeutically effective amount of the angiotensin is sufficient to improve function of the one or more tissues outside the heart and brain.

Problems solved by technology

Although these therapies alleviate symptoms, and may even improve survival, none can reverse the disease process and directly repair the lasting damage.

However, clinical trials to alleviate ischemia were disappointing.

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